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TOR Complex 2-regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain-containing proteins located at plasma membrane-endoplasmic reticulum contact sites

Roelants, FM; Chauhan, N; Muir, A; Davis, JC; Menon, AK; Levine, TP; Thorner, J; (2018) TOR Complex 2-regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain-containing proteins located at plasma membrane-endoplasmic reticulum contact sites. Molecular Biology of the Cell , 29 (17) pp. 2037-2136. 10.1091/mbc.E18-04-0229. Green open access

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Abstract

In our proteome-wide screen (Muir et al. 2014 Elife), Ysp2 (also known as Lam2/Ltc4) was identified as a likely physiologically relevant target of TORC2-dependent protein kinase Ypk1 in the yeast Saccharomyces cerevisiae. Ysp2 was subsequently shown to be one of a new family of sterol-binding proteins located at plasma membrane (PM)-endoplasmic reticulum (ER) contact sites (Gatta et al. 2015 Elife). Here we document that Ysp2 and its paralog Lam4/Ltc3 are authentic Ypk1 substrates in vivo and show using genetic and biochemical criteria that Ypk1-mediated phosphorylation inhibits the ability of these proteins to promote retrograde transport of sterols from the PM to the ER. Furthermore, we provide evidence that a change in PM sterol homeostasis promotes cell survival under membrane-perturbing conditions known to activate TORC2-Ypk1 signaling. These observations define the underlying molecular basis of a new regulatory mechanism for cellular response to plasma membrane stress.

Type: Article
Title: TOR Complex 2-regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain-containing proteins located at plasma membrane-endoplasmic reticulum contact sites
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1091/mbc.E18-04-0229
Publisher version: https://doi.org/10.1091/mbc.E18-04-0229
Language: English
Additional information: This is the published version of record. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10051873
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